Smoke and Mirrors

Smoke and
Mirrors
The EPA's Flawed Study of
Environmental Tobacco Smoke
and Lung Cancer
Gary L. Huber, Robert E. Brockie, and Vijay
K. Mahajan
Recently, the Environmental Protection evidence that exposure to a specific substance
Agency (EPA) completed a report con- or agent results in a specific disease; and (3) evi-
Wit'
cluding that exposure to environmental dence that the specific agent causes the disease
tobacco smoke (ETS)-the residual material in question in a certain measurable dose (accu-
from burning cigarettes that is released into mulative or otherwise) or at a certain level of
indoor air environments by the process of active exposure. For many potentially toxic environ-
!'D
smoking-presents a serious and substantial mental agents, the last two criteria are often, if
public health problem. The EPA bases its con- not almost always, fulfilled through experimen-
clusions not on any definitive set of data demon- tal animal studies. These criteria apply not only
strating causality, but on a generalized "total to carcinogens but, more generally, to any
weight of evidence" that, in aggregate, implied potentially toxic substance that causes any kind
causality to the EPA. In reaching those conclu- of disease.
sions, the EPA ignored classic criteria for The EPA's conclusions regarding ETS, how-
.`3
cause-and-effect relationships employed by the ever, did not satisfy those evidentiary criteria.
scientific community. Instead, the EPA "weighted" selected data in an
Without a clearly established mechanism for attempt to support its conclusions by other
determining causality, declaring that a sub- means. A critical assessment of the validity of
stance in our environment poses a significant the EPA's conclusions, then, requires careful
health risk usually rests upon the convergence understanding of the manipulations by which
of three cornerstones of scientific evidence. evidence was weighted.
These include: (1) evidence from population The EPA report is over 500 pages long and
studies that exposure to the agent is associated contains an unusually large amount of technical
with the development of disease in humans; (2) theory and background information.
Comprehensively reviewing the report in its
Gaiy L. Huber is a professor 01't7 iedicine at University entirety is not possible in this relatively brief
of Texas Health Center in Tyler, Texas. Robert E. space. The purpose of this article is to address
Brockie is at the Presbyterian and Doctors Hospital in the more important parts of the EPA report that
Dallas, Texas. Vijay K Mahajan is a professor of med- pertain to adults who are exposed to ETS. We
icine at St. Vincent's Hospital in Toledo, Ohio. will address other non-cancer respiratory ill-
44 REGULATION, 1993 NUMBER 3
ENVIRONMENTAL TOBACCO SMOKE
nesses in adults, as well as respiratory illnesses understand exactly what ETS is, and, perhaps more
L.,
.`3
in children, elsewhere. For adult nonsmokers, importantly, to understand what it is not. Some
the EPA concluded that "ETS is a human lung reports treat ETS as if it were a simple, discrete
[11
carcinogen, responsible for approximately 3,000 entity. Others consider ETS to be a collection of
lung cancer deaths annually in U.S. nonsmok- several individual or separate constituents, each of
ers. which can be quantified in a given sample of envi-
NC(D
As a nation, we depend on the EPA to under-
f-)'
ronmental air and assessed for risk separately. Still
phi
take risk assessments on many agents in our others have treated the different kinds of tobacco
.'3
environment that might be potentially harmful smoke, including ETS, as if they were all one and
r-.
to us. When the EPA "speaks," enormous weight the same. Although giving some very limited pass-
C.5
is given to its findings. We generally presume ing acknowledgement to the actual nature of indi-
Q..
that its conclusions are based on solid scientific vidual constituents in ETS, the EPA for the most
evidence and are derived by standard scientific part treated ETS as if it were a discrete entity with
Q..
practices. characteristics and health risks assumed compara-
Our presumption would be overgenerous in ble to the smoke that is inhaled from cigarettes by
p..
Q,,
the case of the ETS report, unfortunately. In this active smokers. In other words, the EPA based
case, the EPA's risk assessment is built on the many of its conclusions on an explicitly stated
vii
manipulation of data, ignores critical chemical assumption that because there is an association
r-.
.,.
analyses and key epidemiological data, violates
(IQ
time-honored statistical principles, fails to con-
Z¢-
trol adequately for important confounding influ- In its report on ETS, the EPA did not
ences (factors other than the one studied that
may affect a result or a conclusion) that provide comply with accepted principles of toxi-
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r-+
alternative explanations for its conclusions, and cology, chemistry, and epidemiology,
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violates its own guidelines for assessing and nor with its own guidelines for under-
establishing risk to a potential environmental
r-,
taking cancer risk assessment.
r-+
toxin. It lacks credible quality control and ade-
quate external unbiased peer review. In short, in
its report on ETS, the EPA did not comply with
accepted principles of toxicology, chemistry, between active smoking and lung cancer there
(74
L/'
and epidemiology, nor with its own guidelines must also be a similar association between ETS
for undertaking cancer risk assessment. In fact, and lung cancer.
the conclusions drawn by the EPA are not even The truth is that ETS is not a discrete entity;
'-.
supported by the EPA's own statements. at least not one that can be completely mea-
In critically questioning these matters, however, sured or characterized as such under real-world
CND
we are not saying that exposure to ETS is without conditions using currently available technology.
CI)
rt.
hazard. The data that have been presented in the The residual constituents of ETS change with
,-.
literature, though, simply do not support any defin- time and differ in composition depending on the
C'4
itive conclusions. We believe that reasonable scien- environment in which they are found.
tists could interpret the published literature on ETS Concentrations of constituents also vary widely
with differing opinions. Nor are we suggesting that from time to time and from place to place.
i-+
ETS should not be taken seriously. There are Furthermore, compared to other kinds of tobac-
.'v.
.^S.
almost 50 million active smokers in the United co smoke, only a small fraction of the con-
.-.
States, and the better part of a billion smokers stituents of mainstream smoke and of side-
f..
worldwide. Because of the large number of non- stream smoke potentially present in ETS have
i-`
Q''
smokers who are in contact with active smokers, ever been quantifiably identified in the
concerns about any potential health risks associat- real-world air to which the nonsmoker is
ed with exposure to ETS are very important. It is exposed.
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an issue that deserves resolution by the highest
.-+
quality of data that science has to offer, not by Sources of Environmental Tobacco Smoke
'-r
compromising well-established scientific principles
or by distorting scientific fact. Not all tobacco smoke is the same. Three differ-
;-'
In analyzing the EPA's report, it is important to ent types exist, all of which differ both physical-
(IQ
CATO REVIEW OF BUSINESS & GOVERNMENT 45
ENVIRONMENTAL TOBACCO SMOKE
ly and chemically. The first, mainstream tobacco stream smoke have not been well characterized
and are present in only trace amounts. What
(FD
smoke, is the material that is drawn through the
e-+
`C3
butt, or mouth end, of the cigarette during goes into the respiratory system of the active
active smoking; this is the tobacco smoke that smoker as mainstream smoke, however, is not
i.;
smokers inhale into their lungs. Depending on what comes out as ETS. The inhaled main-
how they inhale, and on whether or not they stream smoke is stripped within the smoker's
hold their breath, active smokers retain within respiratory system of many of its volatile chemi-
¢.'
their lungs somewhere in the range of 40 to 80 cal compounds. What are left then, as ETS, are
percent of the mainstream smoke that they gen- small amounts of residual altered mainstream
erate. The remainder of the inhaled smoke that smoke particulates, saturated with water vapor
is not retained is exhaled as a potential contri- by their passage through the respiratory system
bution to ETS. and dramatically reduced in volatile chemical
Mainstream tobacco smoke is complex. constituents, as well as some gas phase residual
However, standardized and precise methods of constituents.
reproducibly collecting and analyzing main- The second element of ETS, sidestream
C/1
t-]
smoke, is the tobacco smoke that is released
:=a
stream smoke have been established and accept-
around the burning cone from the tip of the
smoldering cigarette between active puffs.
Although several of the constituents of Sidestream smoke is also very complex. While
smoldering, the cigarette burns at a lower tem-
mainstream tobacco smoke have been perature (500 to 600 degrees centigrade) than it
considered, at one time or another, as does during the generation of an active puff (800
the prime suspect allegedly responsible to 900 degrees centigrade). The chemical sub-
for causing lung cancer, no major car- stances in sidestream smoke are similar to
mainstream smoke, but the differences in tem-
a''
cinogen in smoke has ever been estab-
lished. perature and burning characteristics cause sig-
nificant differences in its chemical nature.
.'"
Unlike mainstream smoke, standardized meth-
ed for years. There are over 5,000 well-charac- ods for collecting and assessing the chemical
terized chemical components of mainstream and physical characteristics of sidestream
-CS
smoke that by weight account for over 95 per- smoke do not exist. Regardless of those prob-
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cent of the smoke. Some of these chemical com- lems in measurement, sidestream smoke
7-l
ponents are recognized or designated human appears to be the major source (about 85 to 90
(DD
not
carcinogens; some are anti-carcinogens. percent) of the residual tobacco smoke con-
Although several of the constituents of main- stituents that end up in ETS.
l71
stream tobacco smoke have been considered, at The third element of ETS is the very small
one time or another, as the prime suspect amount of smoke that diffuses out of the ciga-
allegedly responsible for causing lung cancer, no rette through the wrapping paper, as well as the
.'Y
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major carcinogen in smoke has ever been estab- small amount of smoke that comes directly off
lished. Indeed, the National Cancer Institute and of the burning cigarette tip during active puff-
-CS
O.-
other federal agencies spent hundreds of mil- ing. For practical purposes, those contributions
'C3
,,.
(OD
CO
lions of dollars in a decade-long quest for a safe to ETS are negligible.
or less hazardous cigarette. In retrospect, that By weight, mainstream smoke is made up of
program could at best be considered cost-inef- about 70 percent air (drawn in through the ciga-
fective and at worst a failure. The specific car- rette) and about 10 or 11 percent water vapor.
cinogenic needle in the burning haystack of cig- The remaining smoke is a complex mixture of
`CS
arette smoke was never identified. It was hoped thousands of chemicals. Many of the chemical
S.,
that if the cancer-causing factor in cigarettes constituents of tobacco smoke are highly reac-
"'d
could be identified clearly, it could be removed tive molecules that change within microseconds
+.+
gyp
bbl)
to make smoking less hazardous. This turned of their creation and are chemically unstable in
out to be an elusive goal. our environment.
cc!
One hundred thousand or more additional All forms of tobacco smoke have a certain
chemical components believed to be in main- density, defined as the concentration of particu-
46 REGULATION, 1993 NUMBER 3
ENVIRONMENTAL TOBACCO SMOKE
lates in the gas phase. If the particles are not tion systems, only small numbers of tobacco smoke
dense enough to see, then the product usually is residual constituents-in the range now of 50 to
no longer defined as smoke. Compared to the 100 or so-can be detected in environmental air
p.'
F,,
other types of tobacco smoke, inhaled main- under real-world circumstances, and then only at
stream smoke is quite dense; exhaled main- extremely low levels of concentration.
Over 5,000 compounds are identifiable in
Iii
stream smoke is diluted manyfold and usually is
much less dense. Sidestream smoke starts out as mainstream smoke collected under very careful-
V.`
being nearly equally dense near its point of
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ly controlled circumstances immediately as it
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Cad
emission, but as it moves even very small dis- leaves the butt end of a cigarette. More than half
u-+
tances away from the burning cone it is diluted that many compounds are identifiable in side-
V,'
significantly. stream smoke collected as it leaves the burning
ETS, on the other hand, is not dense at all; it is tip of a cigarette. Is it reasonable to assume, as
highly diluted. In fact, the residual constituents of the EPA has apparently done, that all of those
mainstream and sidestream smoke that find their chemical compounds make their way into envi-
+-,
way into the air as ETS are so highly diluted that it ronmental air in a form that we as nonsmokers
is a misnomer to refer to them as smoke per se. The might passively inhale?
residual constituents present are diluted by a factor No, because as they age and become diluted in
+:,
t,"
3''
environmental air, some of the highly unstable
d"17
of thousands. But the EPA elected to equate ETS
''''
with mainstream and sidestream smoke as if they residual constituents of tobacco smoke react chem-
were all one and the same. The EPA simply chose ically, adsorb onto surfaces in the environment,
not to address the fact that ETS has not been well undergo a variety of other changes, or simply
+.+
characterized qualitatively or quantitatively; we do become so highly diluted that they have not been
not even know exactly what is included in ETS.
In essence, the EPA assumed that if relatively
large amounts of mainstream. smoke are dangerous
to active smokers, miniscule amounts will be haz- No scientific literature supports the
ardous to passive smokers. In some ways, that assumption that ETS should be treated
would not be an unreasonable approach if, indeed, as a functional equivalent to main-
nothing were known about the residual con-
stituents of ETS. But something is known-namely, stream smoke.
that certain residual constituents of tobacco smoke
are sometimes present and sometimes not present,
r/1
in infinitesimally small concentrations, in environ- detected by known analytical means. Many of the
mental air where active smoking is present. The
fir' ..G
chemical reactions are completed within microsec-
3-,
assumption that all types of smoke are the same, onds.
however, is not supported by the available scientific The EPA report simply assumed that the poten-
data. This is extremely important, for one of the tially carcinogenic constituents in mainstream and
cardinal rules of environmental toxicology and risk sidestream smoke establish the carcinogenicity of
assessment is to identify the specific chemical (or
.'"
ETS. There are, however, no data available in the
chemicals) of potential concern, because the bio- EPA document or anywhere else to support that
logical responses to specific chemicals are in them- assumption. Independent studies on ETS have not
^C^
selves highly specific. indicated that it is a carcinogen. ETS is not main-
7-.
stream smoke. ETS is not sidestream smoke. What
The Nature of ETS nonsmokers might inhale passively in the presence
of smokers is not quantitatively or qualitatively the
The EPA states quite authoritatively that "ETS is a same material that active smokers inhale from the
complex mix of over 4,000 compounds." The EPA butt end of a cigarette.
states equally clearly that "this mix contains many
known or suspected carcinogens or toxic agents." Dosimetry and Environmental Standards
Both statements are dubious. No scientific litera-
ture supports the assumption that ETS should be An additional inviolable rule of environmental
treated as a functional equivalent to mainstream toxicology is that, in essence, "the dose makes
smoke. Using the most sensitive of analytical detec- the poison." At some dose, every chemical is a
CATO REVIEW OF BUSINESS & GOVERNMENT 47
ENVIRONMENTAL TOBACCO SMOKE
potential poison. Some of our environmental benzo[a]pyrene, and total polycyclic aromatic
chemicals are toxic to humans and about two hydrocarbons. Limited attention is also given to
dozen or so of them are designated as human
175
two additional chemical constituents generally
carcinogens. But potential toxicity and carcino- unique to tobacco-nicotine (and its metabolic
genicity can be offset, for practical purposes, by breakdown product, cotinine) and the group of
f1.
O.,
limiting our exposure to acceptably low levels. compounds known as tobacco-specific
Levels of exposure to airborne environmental N-nitrosamines.
chemicals are usually expressed in terms of the A recent scholarly monograph, published by
°o0
tin
amount of the chemical substance by its unit Guerin, Jenkins, and Tomkins of the Oak Ridge
weight per volume of environmental air-for National Laboratories, comprehensively
example, in milligrams (mg) of the specific reviewed several published sources from which
chemical per cubic meter (m3) of air. For many a wide range of environmental levels of ETS
,,h
`i7
chemicals, the acceptable level of exposure is constituents can be derived. That monograph is
often quite low, expressed as micrograms or the source of the specific values for ETS envi-
nanograms per cubic meter of air. For compara- ronmental constituents cited here. The mono-
tive purposes, a milligram is one one-thou- graph is cited by the EPA report, but curiously
[r1
sandth of a gram, a microgram (pg) is one enough, the data from it are never integrated
one-millionth of a gram, and a nanogram (ng) is into the assessment.
What, then, is the nature of the relative
health hazards for the specific constituents of
ETS listed by the EPA? One such constituent,
formaldehyde, is designated as a potential car-
Essentially everyone in this country is cinogen. Currently popular commercial ciga-
exposed to potentially toxic or carcino- rettes deliver about 20 to 90 micrograms of
genic chemicals every day, but risk is formaldehyde in mainstream smoke and up to
not established by exposure alone. 700 micrograms in sidestream smoke. Those
numbers may seem high, but in comparison to
other environmental sources they are not. Space
heaters and gas ranges, for instance, release
+-v
one one-billionth of a gram. about 20,000 to 40,000 micrograms of formalde-
The simple exposure of humans to a given hyde per hour into our environment.
chemical, even if it is an established carcinogen, Formaldehyde has also been used extensively in
is by itself usually not associated with develop- finishing and bonding wood products, and in
ment of cancer. Essentially everyone in this O..
coat fabrics and insulation products. In certain
country is exposed to potentially toxic or car- closed environments, such as a house trailer,
cinogenic chemicals every day, but risk is not formaldehyde can reach stable environmental
established by exposure alone. Rather, it is concentrations in excess of 5,000 jig/m3.
established through a dose-response relation- Formaldehyde also has been identified as one of
ship; accordingly, there is usually a specified
-CJ
the culprits in "sick building syndrome."
t1,
level of exposure, or dose, that is accepted as at In most buildings, however, the background lev-
least relatively safe. els of formaldehyde that we commonly are exposed
3,o
What do we really know about levels of expo- to in everyday life are in the range of 40 to 50
OHM
sure to ETS? The EPA report states, "Detailed pg/m3. The best of the published data indicate that
chemical characterization of ETS emissions formaldehyde concentrations in ETS are similar to
under conditions more typical of actual smoking background levels and generally, with unusual
S-.
conditions (e.g., using smokers rather than
'r3
exceptions, do not exceed 40 pg/m3. The estab-
smoking machines) are limited." Like the lished "safe" level for environmental exposure to
Emperor's new clothes, not much is actually formaldehyde is 1,500 pg/m3, or several fold the
i-+
f1,
there. The report does list, but only in graphic level attributable to ETS.
form, six constituents of environmental air that Benzene and toluene are also listed by the
are known residual environmental constituents EPA as residual ETS constituents that are
of tobacco smoke, including formaldehyde, potential carcinogens. With high levels of expo-
toluene, benzene, carbon monoxide, sure, they are associated in humans with the
48 REGULATION, 1993 NUMBER 3
ENVIRONMENTAL TOBACCO SMOKE
development of leukemia. With a limited num- 3,000 ng of PAH. Surprisingly, however, proba-
'z7
a04
ber of exceptions, however, leukemia
,.,
bly the sources with the highest PAH levels in
n'-'
has not been consistently linked to active smok- our diet are the leafy vegetables (e.g. lettuce,
ing, let alone exposure to the highly diluted con- spinach, and unrefined grains), which are conta-
centrations of benzene and toluene that are pre-
S].
minated by outdoor deposition from the air.
sent in ETS. Nicotine is more or less unique to tobacco,
Benzene is ubiquitous in our environment, although very small amounts can be found in
and toluene is chemically related to benzene. certain foodstuffs, such as tomatoes. Nicotine,
Gasoline is a primary source of benzene, however, has never been seriously considered a
CAD
toluene, and other related volatile organic chem- carcinogen. Some nitrosamines are also unique
COD
icals (VOCs) in our air, as is outgassing from to tobacco. Nitrosamines are a suspected human
building materials, office activities and office carcinogen, based on animal studies, but their
machines, photocopying, various combustion specific role in human carcinogenesis has
Vii
sources, glue solvents, paint solvents, and the remained controversial. Exposure to ETS resid-
0°°
like. Frequently encountered background con- ual constituents may, under some circum-
centrations of VOCs in indoor air where residual stances, result in the intake of 0.1 micrograms
Vii
constituents of ETS are expected to be found
generally range from 2 to 20 pg/m3. The highest
environmental concentrations of VOCs (100
pg/m3 and greater) are usually associated with Those who are not smokers deserve to
sources other than ETS. Gasoline in the United have a proper, credible risk assessment
States contains up to 2 percent benzene and fill- undertaken that is based on facts and
C.-
'.3
ing one's tank at a self-service gas station may reality, not on tiers of assumptions and
result in higher levels of benzene exposure over
r`3
extrapolations.
a few minutes than would ever be encountered
from ETS exposure for several hours. The estab-
lished acceptable levels of exposure for benzene or less of nitrosamines per day by nonsmokers,
are 30,000 pg/m3 and for toluene are 375,000 a relatively minuscule amount compared to the
pg/m3, values well above (over a thousandfold) 10 to 100 micrograms of nitrosamines ingested
11.
any that might ever be expected from ETS. from food in the average diet each day.
Benzo[a]pyrene (BaP) is another aromatic Like the 50 to 100 other chemical com-
hydrocarbon that has a high level of carcino- pounds that are reported to have been measured
genicity for animals and is a suspected human in ETS, the constituents of ETS that are cited by
rt.
carcinogen. Background indoor environmental the EPA are present only at infinitesimally low
concentrations of BaP generally range in the concentrations in our environment. If any of
neighborhood of 0.1 to 1 ng/m3 without smokers those constituents are, in fact, carcinogenic to
present, and in the range of 0.3 to 1.5 ng/m3 humans at such very low levels, and if they are
'-'
with them. By comparison, outdoor levels of indeed present in our environment from ETS in
U~-
"'S
BaP in heavy traffic in urban areas or in areas concentrations that represent a true health haz-
close to industrial sources are in the 1 to 3 ard, those who are not smokers deserve to know
'"'
'-"
ng/m3 range. Some highly urbanized areas have that and to have a proper, credible risk assess-
>--C
shown polycyclic aromatic hydrocarbons (PAH) ment undertaken that is based on facts and real-
peak levels of 15-50 ng/m3. Standardized safe ity, not on tiers of assumptions and extrapola-
0__
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exposure levels for BaP have not been estab- tions.
lished. Our primary exposure to PAHs, however,
x4.
comes not from our environmental air but from Assessing Health Risks
°!-}
the food we eat and from the water we drink.
Our dietary intake of BaP, for instance, is proba- Because ETS has not been well characterized as
bly about 1,000 to 5,000 ng/day, without any
Z1,
a physical or chemical substance, and because
charcoal-broiled meat. Drinking water contains the level of exposure to most of the residual con-
.-'
1 to 10 ng/L of PAHs and surface waters contain stituents of tobacco smoke in environmental air
several hundred nanograms per liter. One piece is too low to be quantified under real-world con-
of charcoal-broiled meat delivers about 2,000 to ditions, assessing the purported health risks of
C'3
CATO REVIEW OF BUSINESS & GOVERNMENT 49
ENVIRONMENTAL TOBACCO SMOKE
Figure 1 exposed to this variable (lung cancer in non-
90 % CONFIDENCE INTERVALS FOR RELATIVE RISK smokers married to nonsmokers). The resultant
By Country risk ratio or odds ratio is the calculated rate of
disease studied in the exposed population divid-
Greece
ed by the rate of that disease in the unexposed
Hong Kong population, as follows:
Japan F-+-I Rate of lung cancer in nonsmoking
Relative Risk = women married to husbands who smoke
USA
Rate of lung cancer in nonsmoking
Western Europe I- {
women married to husbands who do not smoke
China H {
The terms "risk ratio," "odds ratio," and "rela-
0.0 0.5 1.0 1.5 2.0 2.5 3.0
tive risk" are often used interchangeably, espe-
cially for rare diseases like lung cancer. If the
From EPA, 1992
disease rates in the two populations studied
(nonsmoking women married to smokers versus
passive smoking becomes very difficult. Two of nonsmoking women married to nonsmokers)
the three cornerstones for determining a causal were exactly the same, the odds ratio or relative
relationship-( 1) establishing a specific sub- risk would be 1.0. If more lung cancers occurred
`-'
stance that causes a specific disease and (2) in nonsmoking women married to smoking
$.U
establishing a dose relationship for the develop- spouses than occurred in nonsmoking women
ti'
ment of that disease-cannot be established on married to nonsmoking spouses, the relative risk
.fl
the basis of the data now available. The third
Q.'
would be greater than 1.0.
remaining approach is to evaluate the potential Currently, there are at least 32 published
-fl
studies in the literature that evaluate rates of
'_'
'"'
health risks for nonsmokers in epidemiological
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studies. lung cancer in women as a function of their hus-
Z:? +-'
Epidemiology studies employ statistical band's smoking habits. The first of those studies
'TS
n..
analyses to determine the rate and distribution was published in 1981 and the last two studies
.`3
of a disease (or diseases) within given human
OH"
were published in 1992. Thirteen of the studies
Q.,
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CIA
populations and, when possible, the factors that were conducted in the United States, and 19
are associated with the development of that dis- have come from abroad. Most evaluate rates of
ease. Epidemiology studies are most effective lung cancer in nonsmoking females married to
l~4
when they can assess a specifically defined risk smoking males; one study evaluates data on a
CAD
factor. Because exposure to residual con-
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mixed male and female population; a few con-
stituents of tobacco smoke in our environment tain limited data on nonsmoking males married
CMG
cannot be quantified, epidemiologists have to smoking females. (Those limited data,
,-r
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again had to use indirect measurements, or although mentioned in passing, were not includ-
All
(f0
proxies, of ETS exposure. ed in the EPA's final analysis of lung cancer risk
In its epidemiological risk assessments, the assessment.)
EPA employed previously published studies that All of the studies assume, without measuring or
`CS
evaluated the development, or lack of develop- attempting to quantify, that nonsmoking wives are
cam'
ment, of lung cancer as a function of spousal exposed passively to the residual constituents of
smoking habits. These studies were based on a ETS generated within the home and elsewhere by
concept of "relative risk," usually expressed as their smoking spouses. The studies generally were
O..
an odds ratio. Relative risk expresses statistical based on questionnaire responses; actual levels of
correlations for the rates of disease development exposure to ETS constituents were not determined.
.-+
in two populations; it is defined as the relation- Such questionnaires remain the only data available
`CS
ship of the rate of the development of a disease to assess the specific potential health effects of ETS
V).
(in this instance, lung cancer) within a group of on nonsmokers.
individuals (primarily nonsmoking wives) Outcome measures for studies conducted in
.Y"
exposed to a variable in the population (spousal
.ti
various parts of the world varied considerably (See
.f."
or husband's smoking habits), divided by the
(1.
'C3
Figure 1, above). The reasons are not entirely clear,
CAD
rate of the same disease in individuals not but it is presumed that other lifestyle factors (air
50 REGULATION, 1993 NUMBER 3
ENVIRONMENTAL TOBACCO SMOKE
TABLE I
LUNG CANCER RELATIVE RISKS ASSOCIATED WITH PASSIVE SMOKING
Year Adjusted Recalculated Original CI (95%)
tea:
Study Original Data
EPA Data EPA CI (90%)
Brownson 1987 1.50 (0.48, 4.72) (0.39, 2.97)
r-+
1.68
`-'
Brownson 1992 DNI* DNI* 1.00 (0.8, 1.2)
Baffler
0~0
1984 0.68 (0.32, 1.41) 0.80 (0.34, 1.81)
Butler 1988 2.01 (0.61, 6.73) 2.00 N/A
Correa
.ti
1983 1.89 (0.85, 4.14) 2.07 (0.81, 5.26)
Fontham
e-V
n-i
1991 1.28 (1.03, 1.60) 1.28 (0.93, 1.75)
Garfinkel
n^+
+-i
1985 1.27 (0.91, 1.79) 1.12 (0.94, 1.60)
Garfinkel (0.85, 1.89)
-"+
1981 1.16 (0.89, 1.52) 1.17
Humble 1987 2.00 (0.83, 4.97) 1.78 (0.6, 5.4)#
Janerich
.-r
1990 0.79 (0.52, 1.17) 0.93 (0.55, 1.57)
Kabat 1984 0.73 (0.27, 1.89) 0.90 (0.46, 1.76)
Stockwell 1992 DNI* DNI* 1.6 (0.8, 3.0)
Wu
r..
1985 1.32 (0.59, 2.93) 1.20 (0.50, 3.30)
11 EPA Studies --- 1.19 (1.04, 1.35) ------ ------
DNI (Data Not Included) Data from these studies were not included in the EPA risk assessment
Humble and coauthors were the only U.S. study to report data with confidence intervals of 90%; all other studies
reported their results at the conventional level of 95% confidence intervals
pollution exposure, diet, cooking practices, racial "adjusted" the originally published data, in theory
genetic variation, etc.) are important variables that correcting for potential misclassification of smok-
influence the development of lung cancer. ers as nonsmokers and other factors. Those
ran
Although it tabulated summary data from all "adjustments" were undertaken because question-
"f]
studies worldwide, the EPA based its risk assess- naires regarding smoking habits are notoriously
ment for lung cancer on only 11 of the 13 available limited and often inaccurate, largely because smok-
studies from the United States. Because of the ing has become a social taboo in this country, and
social, cultural, and racial differences that exist active smokers sometimes deny their smoking
car
between widely diverse geographical areas, relying practices when answering questionnaires. For their
only on U.S. studies was a reasonable approach. calculations, the EPA also selected "subsets" of data
S1.
The EPA chose to exclude the two most recent U.S. from the initially reported total data published.
studies, however, simply because they were pub- Table 1 provides both the EPA-adjusted data
lished after an arbitrary cut-off date earlier in 1992. (sometimes representing only subsets of selected
Interestingly, one of the excluded studies, by data) and the original data from the original publi-
Stockwell et al. from the National Cancer Institute, cations.
stated that for lung cancer "we found no statistical-
ly significant increase in risk associated with expo- The Magnitude of the Risk
sure to environmental tobacco smoke at work or
during social activities." A relative risk, or odds ratio, is characterized as
fl)
The odds ratio data from all 13 U.S. studies are strong or weak depending on its magnitude, or
presented in Table 1, above, and are expressed as degree of association. A strong relative risk has an
the estimated value of relative risk. The EPA odds ratio of 5.0 to 10.0 or greater. By conventional
CATO REVIEW OF BUSINESS & GOVERNMENT 51
ENVIRONMENTAL TOBACCO SMOKE
definition, weak relative risks are ones where the the Buffler study as one example from Table 1,
ago
odds ratio is in the range of 1.0 to 3.0 or so. In both the relative risk for developing lung cancer in a
..,
!CD
the original data and in the EPA-adjusted data, all nonsmoker living with a spousal smoker was, by
O''
of the odds ratios are relatively small or weak. the originally published calculation, 0.80. If this
Three of the studies have an odds ratio of less than average value were taken alone, without some
1.0 (potentially suggesting less lung cancer occurs associated statistical test, a "protective" effect
would be implied, based on the average odds
..°
..a
in nonsmokers married to smokers than occur in
Q..
...
nonsmokers married to nonsmokers), and none of ratio. The confidence interval for this study (at
+-`
the studies report a strong relative risk. the 95 percent confidence level), however, was
Could one conclude from these data that 10 of
,.°
0.34 to 1.81. In other words, with 95 percent con-
'-.
the studies demonstrate a small increased relative fidence, the real effect or true value of relative
Q.1
risk for the development of lung cancer on the
^(3
risk for this study was any odds ratio within the
basis of history of spousal smoking and three of
'C3
'C3
range of 0.34 to 1.81, although the distribution
pro
the studies was weighted
demonstrate a around an average
"=7
Figure 2
"protective" effect of 0.80. Interpreted
`-r
on the same 95% Original Confidence Interval for Relative Risk in that way, the
r-+
By Studies from the United States
basis? To answer results have about
phi
that question, sci- as much chance of
,7'
t.0
Brownson i
entists, including showing an
t..
Brownson
epidemiologists, Buffler i-+ i
increased risk as
rely on measure- they do of showing
..+
Butler
ment of what is Correa
decreased risk for
termed "statistical developing lung
(J4
Fontham
significance," cancer as a func-
"'h
Garfinkel
which pertains to Garfinkel
tion of spousal
whether the smoking history.
.-.
;-a
Humble i
observed result is The odds ratio val-
Q.,
Janerich
related to the ues in all of the
('D
Kabat
variable studied ETS studies, how-
Q..
Stockwell I i
(in this instance, ever, are so small
,-,
Wu
a smoking that any other
spouse) and not All Studies (EPA) N1 minor factor could
due to random iii!
't3
H disturb the result.
r-+
i !
}-iI } i i
Any odds ratio
}
variation or mere
..,
'°o
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0
result whose range
O''
chance.
774
Science has of confidence val.-
142
ues reaches or passes through unity or 1.0 (the
SS.
established rules for determining statistical signifi-
'-'
cance. With rare exceptions, scientific convention value of zero increased risk) is considered, by
has established that something is probably "true" if conventional scientific rules, to be statistically
there is no more than a 5 percent chance that the not significant. For a relative risk to be signifi-
result could be attributed to mere chance. One cant, the range of values of the confidence inter-
moo
''"
commonly used statistical assessment of this mea- val must be entirely greater than, or less than, a
.-r
surement of random chance is the confidence reference value of 1.0. The odds ratios and their
,.,
.`S
interval. inclusive confidence intervals for all of the ETS
'v)
A confidence interval is a numerical range of lung cancer studies from the United States are
values that has a specified probability of includ- shown graphically in Figure 2, above. Using the
5C..
t.>
+.i
cry
ing the true value (as opposed to the estimated original results reported for the 13 studies from
the United States, all 13 studies failed to demon-
p..
value) within that range. A 95 percent confidence
(DR
interval indicates that there is a 95 percent possi- strate a statistically significant relationship
.'.
r-'
bility that the observed result did not happen by between spousal smoking and lung cancer in
,.fl
chance, and a 5 percent possibility that the nonsmokers. Using the EPA-adjusted data, 10 of
(1U
observed result was due to chance alone. Using
'LS
the 11 studies employed in the EPA analysis also
U04
52 REGULATION, 1993 NUMBER 3
ENVIRONMENTAL TOBACCO SMOKE
are unable to show a statistically significant
risk.
When a series of epidemiologic data suggest an
effect that sometimes reaches statistical signifi-
cance and sometimes does not, it may prove of
value to combine all of the data from all of the
studies into one comprehensive analysis. That pool-
ing of data is called a "meta-analysis." The EPA
pooled the adjusted results of 11 studies into such a
meta-analysis. The resultant relative risk or odds
ratio for all of these studies' combined values was
1.19, with a 90 percent confidence interval of 1.04
to 1.35. On the basis of the combined pooling of
data or meta-analysis, the EPA concluded that
there was a 19 percent increased chance of devel-
oping lung cancer if you were a nonsmoker mar-
ried to a smoking spouse, although 10 of 11 studies
from which the data were derived revealed no sta-
tistically significant effect even after being adjusted
by the EPA.
Manipulation of Data
P_..°r
for establishing risk.
Is the EPA meta-analysis a scientifically valid A relative risk of 1.19, even if the data were
manipulation of data? Combining data and under- not manipulated, is extremely weak. It is of the
taking a meta-analysis are valid procedures under same general magnitude as the risk that an
;-O
appropriate circumstances. But in order to make American citizen faces of dying in a bicycling
the outcome value of their meta-analysis "valid" accident over the course of a lifetime. It is a risk
and "statistically significant," the EPA first had to that is less than that associated with developing
adjust the data as originally published in colon cancer by drinking chlorinated water,
'C$
peer-reviewed literature and, second, they had to
broaden the confidence intervals to a scientifically
unconventional level of 90 percent.
When a number of studies are combined, the Had the EPA not adjusted the original
confidence intervals generally are "ratcheted data, its analysis would not have had the
same outcome.
'L7
down," or tightened, to assess significance; the EPA
did just the opposite and in so doing diminished its
report's scientific value. Lowering of statistical
S.4
standards to make valid otherwise unmeaningful
results is an unusual and dubious scientific prac- which is in most U.S. cities' water supplies. It is
tice. In the past, the EPA has employed 95 percent generally accepted in the medical literature that
confidence levels as a measure of scientific validity. any time a relative risk is less than 2.0, the dis-
Had the EPA done so in this case, or had it not tinct possibility exists that the finding is artifac-
adjusted the original data, its analysis would not tual and a consequence of the influence of con-
have had the same outcome. If the EPA had includ- founding factors.
ed all of the available published data, and not just For instance, many studies indicate that
CSC
11 of 13 studies, its outcome assessment also would dietary factors alone can influence the rate of
have been different. The manipulation of data in development of lung cancer, both in smokers
this manner to develop statistical significance per- and in nonsmokers, through a relative risk in
p.,
in,
CSC
mitted the EPA to declare passive smoking a Group the range of 20 to 30 percent or so, the same rel-
A carcinogen-the highest rank possible. Without ative magnitude of risk attributed to ETS by the
the recalculations and manipulations, the EPA EPA. Multiple reports from the National Cancer
would have not met any of the three classic criteria Institute and others demonstrate that, because
CATO REVIEW OF BUSINESS & GOVERNMENT 53
ENVIRONMENTAL TOBACCO SMOKE
of their lifestyles, the diets of smokers tend to be ity of science in its risk assessments.
deficient in beta carotene, vitamins A, C, and E, With its document on passive smoking, the
,'3'
Q.,
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folate, selenium, and other nutrients known to EPA disregarded the suggestions of its own
+°.
!3'
C".
be anti-carcinogenic. In addition, smokers have review. Scientific integrity was compromised, if
"C'
lower blood levels of beta carotene and other not outright abused, by the manner in which
(T4
nutrients than can be explained by diet alone. this risk assessment was generated. Abusing sci-
^C7
'ZS
Characteristically, smokers exhibit other high- entific integrity and generating faulty "scientif-
'..
risk behaviors that reflect an unhealthy lifestyle. ic" outcomes through manipulations, assump-
Although the degree to which nonsmoking tions, and extrapolations leads to the develop-
spouses share such high-risk behaviors has not ment of mistaken programs at enormous cost to
been extensively quantified and is currently our government and to taxpayers. Indeed, the
under study, it is only common sense that many cost to the scientific process itself is even
of the various risks, especially the dietary ones, greater. Science should dictate what policies
S1:
might be shared. need to be established; predetermined policies
N¢?
As individuals grow older, they have an should not dictate how science should be inter-
N.3
increased risk for the development of lung can- preted. We have many problems in the environ-
cer, as well as other cancers. Age, then, becomes ment, some of which are of far greater biologi-
a very important confounding variable in any
."3"
cal impact than our potential exposure to the
':5
study that evaluates the effect of an environmen- residual constituents of ETS. The EPA is
775
tal agent on the development of lung cancer. charged with addressing those problems critical-
.fl
,-,
'.3
The EPA analysis, as well as some of the original ly, objectively, and honestly. Compromising the
reports, did not control for this important vari- credibility of the EPA by adjusting science
'L7
able. leaves us with an important resource substan-
+.'
y°°
There are more than 20 other confounding tially diminished. We need and we deserve bet-
'-O
v,'
factors that have been identified as important to ter. Will reality and fact ever catch up with polit-
assessing risk for lung cancer. When the sug- ical science at the EPA?
C1,
(A.
'.v
gested relative risk is very low, as it is in passive
V)'
:,,
smoking, a single uncontrolled or unaccounted
a1)
variable can cause a totally spurious interpreta-
tion. The EPA's risk assessment acknowledged
Selected Readings
that confounders are important to any evalua-
'C3
`ti
tion of ETS as a potential carcinogen. Its con-
cern for confounders was extremely limited, United States Environmental Protection
Agency Office of Health and Environmental
however, and their influence was evaluated by
N,,.
employing a modeling of data by a method as
Assessment, Office of Research and
Development. Respiratory Health Effects of
yet untested and unproved by conventional peer
Passive Smoking: Lung Cancer and Other
review. The EPA, in essence, ignored its own
Disorders. Washington D.C.: 1992.
guidelines and established requirements to rule
"a_ ...
Loehr, R.C., Goldstein, B.D., Nerode, A.,
out confounding as an alternative explanation
Q,'
for an association before basing causal inference
Risser, P.G. Safeguarding the Futures:
+°.
Credible Science, Credible Decisions. (The
on epidemiologic results. Until studies take Report of The Expert Panel on the Role of
these variables into consideration, we will never
Science at EPA.) Cincinnati: Center for
know the true risks of ETS exposure.
(!1
Environmental Research Information, U.S.
Environmental Protection Agency, 1.992.
Safeguarding the Future
C!]
Guerin, M.R., Jenkins, R.A., Tomkins, B.A. The
poi
Chemistry ofEnvironmental Tobacco Smoke:
The EPA, apparently at its own request, recently
Composition and Measurement. Chelsea,
underwent a review to identify how it could bet-
Michigan: Lewis Publishers, Inc., 1992.
ter use sound science as a foundation for its pol- Huber, G.L., Brockie, R.E., Mahajan, V.K.
icy decisions. That review, published as
"Passive Smoking: How Great the Hazard?"
"Safeguarding the Future: Credible Science,
'-n
Consumers' Research. Vol. 74, No. 7, July
Credible Decisions," was critical of the EPA, and
Vii
1991.
included a set of guidelines to improve the qual-
54 REGULATION, 1993 NUMBER 3